PML School: Custom PK/PD Modeling Made Easy

PML School: Custom PK/PD Modeling Made Easy

In our increasingly noise-filled world, sometimes, the most powerful insights come from listening. As the head of support at Certara, I get excited about listening to our clients’ pharmacokinetic/pharmacodynamic (PK/PD) modeling dilemmas and helping them solve them. And through listening to our users who call our support hotline, attend our training courses, or participate in our Phoenix Roadshow events, I realized that they were struggling with our Phoenix Model engine. They needed a library of dedicated models and hands-on experience using them to take advantage of this powerful technology. By listening to our user’s concerns, the idea for PML School was born.

PML School is a twice-monthly series of webinars around PK/PD Modeling with Phoenix WinNonlin where we illustrate how to build custom PK and PK/PD models. We started the series this September. Judging by the hundreds of users who attend each session, we seem to have struck a chord that resonates with our users.

Maybe you’re wondering what PML stands for? Phoenix Modeling Language (PML) is the language that runs the Phoenix modeling engine. Typically, learning a modeling language is a tedious and lengthy exercise. And for beginners, learning a modeling language can pose a high barrier to entry. But for the Phoenix Modeling Language, this need not be the case. Our goal for PML School is to lower the barrier to entry and quickly turn new modelers into happy users.

PML School’s step wise approach to model building shortens your learning time and gets you modeling fast!

Phoenix model object UI

Everything is connected in the Phoenix model object’s user interface. Whether working with built-in options or the graphical model, the model engine always executes the textual model. The built-in options and graphical models are just alternative representations of the textual model. When building a new model, start with the built-in options to choose the number of compartments, the route of administration, etc. The built-in options support building a variety of models. When you have exploited all built-in options, switch to the graphical model builder to add additional compartments, observations, flows, parameters or procedures, just by picking from the menu. The final step is fine tuning the textual model. In each PML School webinar, we explain the requirements and syntax of the textual model. Frequently, you only need to make a few tiny changes to the textual model. But, you need to understand these subtleties to build robust, custom PK/PD models.

The PML School curriculum covers 20 common modeling scenarios. We are grateful to Drs. Johan Gabrielsson and Dan Weiner for giving us permission to use exercises from their book, Pharmacokinetic and Pharmacodynamic Data Analysis, to illustrate these models. Their book has recently been released in its 5th edition and is a standard for PK/PD modeling. It explains the theory of PK/PD modeling and provides more than 100 detailed exercises covering a range of modeling scenarios. The book also comes with a memory stick containing all the exercises in the form of Phoenix project files. We have been granted permission by the publisher to present 20 of these exercises in webinars and provide the models in text form.

To select the models featured in PML School, we reviewed all support cases received over the past four years. We assigned each modeling question to relevant exercises in the book. Then, we ranked all exercises according to the frequency of associated support cases. From this ranking, we selected the top 10 PK as well as the top 10 PD models.

PK Models PK/PD Models
3-compartment model PK/PD link
multiple dose Hill model, logistic model
parent metabolite kinetics tumor growth inhibition
IV/PO, simultaneous fit enzyme inhibition
Michaelis-Menten PK/PD link, initial estimates
dose escalation warfarin
multiple dose indirect response, dose escalation
target-mediated drug disposition (TMDD) multiple dose, indirect response
zero order absorption dose response, dose escalation, ED50
allometric scaling transduction, transit compartments
enterohepatic recirculation

We are presenting the exercises in individual webinars on a biweekly basis through August 2017. After each webinar, we post the materials to the Certara Forum in the newly created PML School category. Webinar registrants will be given a link to the recorded webinar as well as the presentation slides. We will also provide access to the textual model as a downloadable text file. These text files can be imported into Phoenix for use with different data sets. I hope that you’ll visit the forum to post your questions and comments on the webinars! Let’s start an ongoing dialogue.

So far, PML School has generated an overwhelming positive response from a large group of users. Join us at upcoming webinars to accelerate your ability to develop complex models that address critical drug development problems.

Accelerate your ability to build custom PK/PD models!

To learn more about how model-informed drug development can leveraged to  relieve the in vivo constraints of sequentially answering core drug development questions by building parallel but connected in vivo and in silico development paths, watch this webinar by Certara CEO Dr. Edmundo Muniz.

Bernd Wendt

About the Author

Dr. Bernd Wendt has been teaching as a trainer at Certara and is a lecturer at the Ludwig-Maximilians-Universität (Munich) for more than 5 years, providing seminars in pharmacokinetics and molecular modeling. He is currently heading the global support group at Certara.